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G Rossolini

Publications and source records attributed to G Rossolini.

At least 19 recordsLinked to original sources
PubMed2001

Use of mathematical models of survivorship in the study of biomarkers of aging: the role of heterogeneity.

An ever increasing number of people have been engaging in aging research using various interventions aimed to modify aging processes, and/or life span, of experimental animals. Since this type of studies needs outcome parameters for assessing the efficacy of such interventions, research on biomarkers of aging (ABs) has received new stimuli. In the present paper, the problem of the occurrence of a vicious circle any time we study ABs and determinants of aging is addressed. In fact, while ABs would represent the standard reference to be used in the study of the main causes of processes of aging, these very determinants should already be known in order to get reliable ABs. A feasible way to overcome this impasse is proposed, using mathematical models of survivorship or mortality based on biological hypotheses and accounting for inter-individual heterogeneity, a necessary ingredient for a correct interpretation of survival results. Specific kinetics of experimental parameters that are candidates as ABs can be compared to the kinetics hypothesized for general biological functions entering the model. We have built a model of this type that can also be used to perform a reliable overall gross estimate of the rate of aging, R(a), in the population, a parameter useful when judging the success of interventions aimed to act on determinants of aging. The perspective that theory of complex systems can be of help in the search for ABs is also discussed.

Aging↗
PubMed2001

Long-live euthymic BALB/c-nu mice. I. Survival study suggests body weight as a life span predictor.

This paper is the first of a series aimed to show the main physiological and pathological characteristics of male euthymic BALB/c-nu mice, a long-live strain of BALB/c mice bred in our own Institute. In particular, the first two paired papers are respectively devoted to general survival information and disease characteristics, also taking into account very old animals that are of high interest for studies on successful aging. In this paper we report the analysis of survival kinetics, the time course of body weight and the correlation between body weight and time-at-death. The longitudinal study has been performed on 88 male mice, checking individually their body weight and date of death and analyzing survival data by a model built by our own. Survival analysis shows quite higher longevity (median age: about 29 months) in this population when compared with other BALB/c strains. The most relevant finding on body weight is its correlation with longevity until the age of 22 months: thinner subjects live longer and lose weight at a lower rate than their heavier mates. Results have formed the basis on which to plan the cross-sectional experiment to study pathologies and biological parameters at different ages, including a group of mice at very advanced ages (34 months).

Animals↗
PubMed2001

Long-live euthymic BALB/c-nu mice. II: spontaneous tumors and other pathologies.

This paper is the second of a series aimed to show the main physiological and pathological characteristics of male euthymic BALB/c-nu mice, a long-live strain of BALB/c mice bred in our own Institute. The previous paired paper Piantanelli (Mech. Ageing Dev. (2001)) has been devoted to a survival study up to advanced ages highly interesting for studies on successful aging. In the present paper we report first data of a cross-sectional study on 4,15,22,28 and 34 months-old mice, dealing with tumors and other relevant pathologies. Results have shown that tumors or other pathologies can hardly be detected up to the age of 22 months. At 34 months of age about 40% of mice revealed a variety of neoplasia and other diseases are clearly detectable. These results suggest that a significant increase in longevity could be a factor increasing the risk of tumor development; thus, caution has to be paid in studies on mice utilized for long term carcinogenicity assay, where animals are sacrificed at the age of 18 months, according to the International Program. Finally, animals of the same chronological age have been subdivided in clusters according to their presumptive longevity, estimated taking advantage of the relationship between body weight and age-at-death found in the paired longitudinal study. This subdivision will be helpful in interpreting inter-individual variability of the biological parameters checked in these animals.

Aging↗
PubMed2001

Mathematical modeling of the aging processes and the mechanisms of mortality: paramount role of heterogeneity.

Main problems of modeling the link between aging processes and mechanisms of mortality are addressed. Various applications of Gompertz's law, which allowed to formulate some fruitful hypotheses on the field, are reviewed. Some pitfalls occurring in its applications are also discussed using a model built on purpose to overcome these difficulties. The role played by heterogeneity emerges as the common cause of some relevant failure in using Gompertz's law and the necessary key ingredient of any model aimed to interpret the link between aging and mortality correctly. Though a number of problems are related to inter-individual variability, the search for their solution can lead to an intriguing approach to the study of aging and mortality. Living beings can be considered as complex systems and their age-related changes can be described at the light of complex system theory.

Aging↗
PubMed2001

Gut neuroendocrine cells: relationship to the proliferative activity and apoptosis of mucous epitheliocytes in aging.

OBJECTIVES: Diffuse neuroendocrine system (DNES) cells regulate homeostasis via neurocrine, endocrine and paracrine mechanisms. Extensive effects of peptide hormones and biogenic amines necessitate studying of DNES cell biology in aging. In this connection, the functional morphology of gut neuroendocrine cells (NEC), proliferative activity and apoptosis of mucous epithelial cells in aging have been studied. MATERIAL AND METHODS: The study was performed on BALB/c-nu mice of 4, 21 and 34 months of age. NEC, proliferative activity and apoptosis of mucous epitheliocytes in stomach and duodenum have been studied by histochemical, immunohistochemical and morphometrical methods. RESULTS: The total number of NEC shows an increasing trend with advancing age. However, the different types of NEC elicit differential patterns. The total number of epithelial cell nuclei does not show any statistically significant difference during aging. The proliferative activity of mucous epitheliocytes also shows no difference among the three animal groups studied. On the contrary, the apoptotic index increases with advancing age. CONCLUSIONS: The results demonstrate that various gut NEC show differential behavior with age and their time-courses are dependent on the site of location (stomach or duodenum). The picture seems quite complex to allow a comprehensive interpretation, nonetheless it gives us some useful indications for further investigation. In fact, since the gut does not show evident gross age-related physiological changes, modifications with age in specific biological parameters can suggest the key mechanisms of compensative regulatory processes possibly acting during aging.

Aging↗
PubMed2000

Neurochemical parameters of the main neurotransmission systems in aging mice.

The present work was designed to study the effect of aging on some parameters of the glutamatergic, aminergic and cholinergic neurotransmission, in the main brain areas of mice of the long-surviving BALB/c-nu strain. We have assayed: (1) the density of three ionotropic receptors for excitatory aminoacids (EAA) which selectively bind kainic acid (KA), N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA); (2) the content of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) and the levels of the DA metabolite dihydrophenylacetic acid (DOPAC) and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA); (3) the level of the choline acetyltransferase (ChAT), the enzyme catalyzing the synthesis of acetylcholine. The parameters were measured in animals at the age of 6, 12, 18 and 24 months; the brain zones under test were the frontal cortex (FC), the corpus striatum (STR), the hippocampus (HIP), the medio-dorsal cortex (DC) and the cerebellum (CER). Significant age-related variations for the density of KA-type and NMDA-type receptors were found in STR and a decrease of the NMDA parameter was found in DC. Neither the monoamine and metabolite contents nor the ChAT levels showed any significant variation in all the tested areas. These findings suggest that an unbalance among different neurotransmission activities could take place with normal aging in rodents: it could be involved in the onset of the motor deficit which occurs in the elderly of these and other mammals.

Journal Article↗
PubMed1998

Reduced DNA synthesis in primary cultures of hepatocytes from old mice is restored by thymus grafts.

We previously observed in vivo that a neonatal thymus grafted into old mice can correct age-related changes such as occurrence of hepatocyte tetraploid nuclei and impaired isoproterenol-induced DNA synthesis in submandibular glands. The aim of the present paper was to study the influence of age and thymus on basal and beta-adrenergic-stimulated DNA synthesis using primary cultures of mouse hepatocytes. In the absence of any adrenergic agents, cells from young mice show peak DNA synthesis between 36 and 48 h; old mice show a similar time course, but the peak is significantly reduced statistically. The main result is represented by the behavior of hepatocytes from old thymus-grafted mice, which recover the levels of [3H]-thymidine incorporation toward young-like values. Grafted animals also show a correction of total DNA content that is increased in old mice. The addition of isoproterenol does not modify the DNA synthetic pattern, whereas the antagonist propranolol causes a slight but statistically significant decrease.

Adrenergic beta-Agonists↗
PubMed1993

Use of a new mathematical model in fitting survivorship curves of Drosophila treated with the antioxidant thiazolidine carboxylic acid.

We have recently proposed a mathematical model of survival mortality kinetics. It is based on biological and statistical hypotheses and is able to fit survivorship curves even at advanced ages, where other models fail. The mathematical function contains two parameters, omega and So, related to deterministic and stochastic factors, respectively. In the present paper the model has been applied to a set of survival curves of Drosophila melanogaster. The different curves derived from populations of flies treated with different doses of the antioxidant thiazolidine carboxylic acid (TCA). The treatment induced a significant progressive increase of mean and maximum lifespan up to the TCA dietary concentration of 0.3%. Higher doses of TCA, on the contrary, were toxic, reducing both mean and maximum lifespan. An interpretation of the differential TCA effects has been attempted on the basis of the values assumed by the two model parameters.

Aging↗
PubMed1992

Age-related alterations of isoproterenol-stimulated adenylyl-cyclase activity are partially corrected by thymic graft.

Previous experimental results have demonstrated progressive impairments in beta-adrenergic responsiveness with advancing age. Beta-adrenoceptors are involved in the alterations as their density progressively decreases during aging. Alterations in both in vivo responsiveness and receptor density are corrected by neonatal thymic grafts. In the present paper adenylyl-cyclase (AC) activity has been studied in the same animal models used before. Results show that no statistically significant changes can be observed when AC is assayed in absence of beta-adrenergic stimulation. On the contrary, when assayed after Isoproterenol stimulation, AC activity shows a shift of the peak and a decrease of its height in aged animals. A neonatal thymus grafted into old recipients one month before the experiment was performed, is capable of correcting the altered height of the peak but not the peak concentration.

Adenylyl Cyclases↗
PubMed1992

Modelling survivorship kinetics: a two-parameter model.

A mathematical model of survivorship kinetics is presented. It takes into account both deterministic and stochastic aspects of survival curves. Earlier reports [Piantanelli: Arch Gerontol Geriatr 1986;5:107-118; Piantanelli: Ann NY Acad Sci 1988; 521:99-109] described a model capable of making distinct predictions on the mean and standard deviation of an index of physiological function, fitting data even in the tail of survivorship curves, and accounting for the selection of the cohort at advanced ages. However, it contains four parameters whose biological interpretation is unclear. In the present paper we propose a modification of the model which maintains the main characteristics of the previous one and, in addition, results in two significant improvements. First, the number of free parameters is reduced to only two, making much easier both their estimation and interpretation, particularly when the model is applied to data from various animal groups manipulated in different ways. Second, it is possible to relate the parameters to well-defined deterministic and stochastic factors: specifically, a deterministic component describing the environmental and genetic influence on physiological functions, and a stochastic component representing the fluctuating interactions of the living organism and its environment.

Aging↗
PubMed1991

Role of triiodothyronine in down-regulation and recovery of lymphocyte beta-adrenoceptors in thyroidectomized patients.

Thyroid function modulates beta-adrenergic sensitivity through the regulation of beta-adrenoceptor density. In particular, thyroidectomy decreases and thyroid hormone injections increase beta-adrenoceptor density on human lymphocytes. In the present paper the relationship between receptor modifications and thyroid hormone levels has been studied in human lymphocytes from patients after thyroidectomy. The patterns of early changes as well as recovery trends have been investigated. Results show a statistically significant fall in receptor density, parallelled by a decrease in T3 levels, 1-3 days after thyroidectomy. Recovery of receptor density is observed 5-8 days after surgical intervention and is accompanied by increased T3 levels. There is a positive correlation between receptor density and T3 levels. On the contrary, no statistically significant correlation was observed for receptor density and T4 levels. The time course of disappearance and recovery of receptor density and that of T3 levels have also been analyzed with the aid of a mathematical model fitting experimental data. On this basis, the hypothesis that both down-regulation and subsequent recovery of beta-adrenoceptor density are driven by the fall and rise of T3 is suggested. Data are also discussed in relation to experimental results we have obtained in animal studies.

Adult↗
PubMed1991

Thymus-induced recovery of age-related decrease of brain cortex alpha- and beta-adrenoceptors.

It has previously been demonstrated that thymus exerts a regulatory influence on beta-adrenergic system during aging. In particular, it has been shown that thymus can correct the beta-adrenoceptor density decrease in old mice. In the present paper results of experiments are reported dealing with the influence of the thymus on alpha-adrenoceptors of mouse brain cortex. Both subtypes of alpha-adrenoceptors are studied separately, using different labelled ligands. Results show that alpha 1-adrenoceptor density decreases in old animals, while alpha 2-adrenoceptor density does not change significantly. A neonatal thymus grafted into old recipients is capable of correcting the alteration observed in old mice. The differential impairment of alpha-adrenoceptors resembles that one previously observed on beta-adrenoceptors, where beta 1-type decreases in number during aging with a parallel decrease of adenylyl-cyclase activity, while beta 2-type remains unchanged.

Adenylyl Cyclases↗